The present invention relates to microneedle structures and, in particular, it concerns a microneedle production method and the microneedle structure produced thereby.
Much research has been directed towards the development of microneedles formed on chips or wafers by use of micro-machining techniques. This approach promises the possibility of producing numerous, very small needles which are sufficient to form small perforations in the dermal barrier, thereby overcoming the molecular size limitations of conventional transdermal patches, while being safe for use by unqualified personnel. Examples of such work may be found in PCT Publication No. WO 99/64580 to Georgia Tech Research Corp., as well as in the following scientific publications: xe2x80x9cMicro machined needles for the transdermal delivery of drugsxe2x80x9d, S. H. S. Henry et al. (MEMS 98, Heildelberg, Germany, January 1998); xe2x80x9cThree dimensional hollow micro needle and microtube arraysxe2x80x9d, D. V. McAllister et al. (Transducer 99, Sendai, Japan, June 1999); xe2x80x9cAn array of hollow micro-capillaries for the controlled injection of genetic materials into animal/plant cellsxe2x80x9d, K. Chun et al. (MEMS 99, Orlando, Fla., January 1999); and xe2x80x9cInjection of DNA into plant and animal tissues with micromechanical piercing structuresxe2x80x9d, W. Trimmer et al. (IEEE workshop on MEMS, Amsterdam, January 1995). The more recent of these references, namely, the Georgia Tech application and the Chun et al. reference, disclose the use of hollow microneedles to provide a flow path for fluid flow through the skin barrier.
While hollow microneedles are potentially an effective structure for delivering fluids across the dermal barrier, the structures proposed to-date suffer from a number of drawbacks. Most notably, the proposed structures employ microneedles with flat hollow tips which tend to punch a round hole through the layers of skin. This punching action tends to cause damage to the skin. Additionally, the punched material tends to form a plug which at least partially obstructs the flow path through the microneedle. This is particularly problematic where withdrawal of fluids is required since the suction further exacerbates the plugging of the hollow tube within the microneedle. The flat ended form of the needles also presents a relatively large resistance to penetration of the skin, reducing the effectiveness of the structure.
A further group of proposed devices employ microneedles formed by in-plane production techniques. Examples of such devices are described in U.S. Pat. No. 5,591,139 to Lin et al., U.S. Pat. No. 5,801,057 to Smart et al., and U.S. Pat. No. 5,928,207 to Pisano et al. The use of in-plane production techniques opens up additional possibilities with regard to the microneedle tip configuration. This, however, is at the cost of very limited density of microneedles (either a single microneedle, or at most, a single row of needles), leading to corresponding severe fluid flow rate limitations. The very long proposed needle (about 3 mm) of Smart et al. suffers from an additional very high risk of needle breakage.
Co-pending U.S. patent application Ser. No. 09/589,369, which is unpublished at the date of filing this application and which does not constitute prior art, proposes an improved out-of-plane hollow microneedle structure having an aperture which is located behind a non-hollow piercing tip. The application describes a number of production techniques for such structures, including techniques based upon either dry etching or by combining wet etching techniques with asymmetric abrasion.
While the techniques described in the aforementioned co-pending application produce highly effective microneedle structures, various disadvantages are encountered while implementing such techniques in commercial production. Firstly, conventional deep reactive ion etching (DRIE) is generally sufficiently inaccurate to reduce the usable yield to unacceptably low proportions. Accuracy can be greatly improved by using cryogenic dry etching techniques. This option, however, greatly reduces the rate at which material can be etched away. As a result, these techniques are inefficient for processing large areas of a wafer. Wet techniques, on the other hand, are efficient for simultaneous processing of large regions of a wafer and offer high accuracy. Wet techniques are not, however, suited for directly achieving the asymmetrical forms required for implementation of the microneedles.
A further shortcoming of microneedle structures made by micromachining techniques is the brittleness of the resulting microneedles. Microneedles made from silicon or silicon dioxide are highly brittle. As a result, a significant proportion of the microneedles may fracture due to the stresses occurring during penetration, leaving fragments of the material within the tissue. Furthermore, oblique insertion by an unskilled person could lead to fracture of a very large proportion of the needles, resulting in malfunction of the device.
There is therefore a need for a method for producing hollow microneedles which would combine the advantages of dry and wet etching techniques to offer an effective and reliable production technique. It would also be highly advantageous to provide microneedle structures produced by such production methods.
The present invention is a method for producing hollow microneedles using a sequence of dry and wet etching techniques, and a hollow microneedle structure produced by such techniques.
According to the teachings of the present invention there is provided, a method for processing a wafer to form a plurality of hollow microneedles projecting from a substrate, the method comprising the steps of: (a) forming by use of a dry etching process a plurality of groups of recessed features, each group of recessed features including at least one slot deployed to form an open shape having an included area and at least one hole located within the included area; (b) coating internal surfaces of the holes and the slots with a protective layer; (c) performing an anisotropic wet etching process in such a manner as to remove material from outside the included areas while leaving a projecting feature within each of the included areas; and (d) removing the protective layer.
According to a further feature of the present invention, the open shape is substantially a V-shape formed from two substantially straight slots.
According to a further feature of the present invention, the V-shape is modified by a minimum radius of curvature at the intersection of the two substantially straight slots.
According to a further feature of the present invention, the two substantially straight slots subtend an angle of between about 60xc2x0 and about 120xc2x0 therebetween.
According to a further feature of the present invention, the two substantially straight slots subtend an angle of between about 85xc2x0 and about 95xc2x0 therebetween.
According to a further feature of the present invention, the dry etching process employs deep reactive ion etching.
According to a further feature of the present invention, the dry etching process includes cryogenic dry etching.
According to a further feature of the present invention, a minimum transverse dimension of the hole is greater than a minimum transverse dimension of the slots such that the hole extends to a depth greater than the slots.
According to a further feature of the present invention, a plurality of connecting holes are formed penetrating into a face of the wafer opposite to the projections such that the each of the connecting holes interconnects with a corresponding one of the holes to form a through channel for fluid flow.
According to a further feature of the present invention, the wet etching process employs a solution containing potassium hydroxide.
According to a further feature of the present invention, the wet etching process is performed in such a manner as to selectively remove material from within the included areas such that each of the projecting features exhibits an inclined upper surface sloping upward from the substrate.
There is also provided according to the teachings of the present invention, a microneedle structure integrally formed so as to project from a surface of a wafer, the surface corresponding substantially to a  less than 100 greater than  crystallographic plane, the microneedle structure comprising: (a) at least one wall standing substantially perpendicular to the wafer surface; (b) an inclined surface corresponding to a crystallographic plane and extending from the wafer surface to an intersection with the at least one wall; and (c) a fluid flow channel extending from the inclined surface through to an opposing face of the wafer.
According to a further feature of the present invention, the at least one wall includes at least two substantially straight wall portions together forming a V-shape.
According to a further feature of the present invention, the at least one wall further includes a curved portion interconnecting the at least two substantially straight wall portions.
According to a further feature of the present invention, the two substantially straight wall portions subtend an angle of between about 60xc2x0 and about 120xc2x0 therebetween.
According to a further feature of the present invention, the two substantially straight wall portions subtend an angle of between about 85xc2x0 and about 95xc2x0 therebetween.
According to a further feature of the present invention, the inclined surface corresponds substantially to a  less than 111 greater than  crystallographic plane.